This multi-disciplinary research program is dedicated to gaining an understanding of the relationship between hazardous substances in the environment and their impact on human health. The program's projects and cores focus on the development of new biomarkers of toxic exposures and susceptibility, the causes of childhood leukemia, arsenic-related health effects, quantification of chemical exposures, fate and transport of chemicals in the environment, hazardous waste remediation, and children's health. Specifically, we propose: 1) To develop, validate, and apply biomarkers in studies of human carcinogenesis and reproductive damage; 2) To better understand the impact environmental exposures have on children's health, including susceptibility to leukemia and arsenic-related health problems; 3) To enhance our knowledge of how paternal exposures can lead to spontaneous abortions and developmental abnormalities in the offspring; 4) To expand our ability to measure and predict exposures to toxic chemicals through the optimized use of biomarkers, site monitoring, characterization, and modeling; 5) To improve the efficacy and safety of hazardous waste remediation technologies, including incineration and bioremediation; and, 6) To promote the exchange of information among scientists, regulators, and affected communities so that basic research addresses the greatest needs and produces maximum benefits. A highly interactive, multi-disciplinary program is proposed to achieve these goals that builds upon the successes of the current program.